Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.6.1.44 (AGT)
770 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Genetic polymorphisms of the renin-angiotensin system (RAS) have been associated with coronary artery disease (CAD) but no relation between these polymorphisms and coronary atherosclerosis has yet been systematically evaluated. The CORGENE study is a cross-sectional study involving 463 Caucasians who underwent standardized coronary angiography for established or suspected CAD [156 patients with a previous myocardial infarction (MI), 307 without MI]. Four angiographic scores assessing the extent and severity of the coronary lesions were obtained from a double visual analysis of each angiogram, arbitration being achieved by a quantitative measurement. Three different genotypes were analyzed: the angiotensin I-converting enzyme insertion/deletion (ACE I/D) polymorphism, the Met to Thr change at position 235 of the angiotensinogen gene (AGT M235T) and the A to C transition at position 1166 of the angiotensin II type-1 receptor gene (AT1R A1166C). No significant association was observed between these polymorphisms and the clinical characteristics of MI and non-MI subjects. While most classical risk factors were positively correlated with the angiographic scores, no significant relationship could be established with the three genotypes (r ranging from -0.08 to 0.05). Only one significant correlation was observed: between the presence of the AGT 235T allele and the extent of the coronary lesions (r = -0.19, P = 0.04) in patients with low-risk status. These overall results are not in favor of a role of these RAS genetic polymorphisms in the development of coronary atherosclerosis.
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PMID:Genetic polymorphisms of the renin-angiotensin system and angiographic extent and severity of coronary artery disease: the CORGENE study. 900 97

The Keewatin Inuit of the Northwest Territories of Canada have a very low age-adjusted mortality rate from coronary heart disease. We hypothesized that this apparent protection from disease has a genetic basis. We determined the prevalence of the disease-associated alleles of five candidate genes for atherosclerosis-related phenotypes. Surprisingly, four of the five alleles studied, namely AGT T235, FABP2 T54, PON R192 and APOE E4, were significantly more frequent in a sample of 175 Keewatin Inuit than among a representative control sample of whites living in the region. The high frequencies of these disease-associated alleles suggests either that they have no relationship with disease susceptibility in the Inuit, or that some unmeasured genetic and/or environmental factors mitigate disease susceptibility that is associated with these alleles. This highlights the difficulty in extrapolating findings from one population to another. Also, very modest genotype-phenotype associations were observed between APOE genotype (P = 0.016) and plasma low-density lipoprotein cholesterol concentration and between FABP2 genotype and plasma 2-h postprandial, glucose concentration (P = 0.048). The relationship between APOE alleles and plasma low-density lipoprotein cholesterol was the same as has been previously reported in many study samples. However, the relationship between FABP2 alleles and plasma 2-h postprandial glucose concentrations was the opposite to that reported in other studies. This suggests that differences in environment, such as the type of fatty acid consumed, interacts with functional differences in gene products involved in candidate metabolic pathways to produce phenotypic differences.
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PMID:Are Canadian Inuit at increased genetic risk for coronary heart disease? 918 78

In this investigation associations of gene complexes consisting of seven candidate for coronary atherosclerosis (ACE, AGT, NOS3, APOA1, MTHFR, PLAT, F13) with risk factors for CAD (lipid levels, blood pressure, body mass index (BMI)) were studied in Russian population. 94 male patients with CAD proven by angiography and 131 healthy individuals were involved in the case-control study. We observed a significant contribution of gene combinations ("ensembles"). ACE-MTHFR, ACE-F13, ACE-AGT-MTHFR in the variability of the total cholesterol and LDL-cholesterol levels. The "Ensembles" ACE-AGT-MTHFR were associated with variability of three atherogenic risk factors (LDL, BMI, cholesterol total). Two-locus gametic disequilibrium was analysed between gene polymorphisms. NOS3 and ACE, NOS3 and APOA1 were in gametic disequilibrium in the control group. Polymorphic markers of ACE and F13, NOS3 and F13, ACE and PLAT loci were in gametic disequilibrium in the patients. Both approaches (association analysis and gametic disequilibrium) revealed the same gene combinations contributing to the CAD risk factors. NOS3 and APOA1 markers were in gametic disequilibrium in the patients and both of them were associated with LDL. F13 and AGT were associated with systolic and diastolic blood pressure and two-locus gametic disequilibrium between F13 and AGT polymorphisms observed in the patients.
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PMID:The estimation of gametic disequilibrium between DNA markers in candidate genes for coronary artery disease (CAD) and the associations of gene complexes with risk factors for CAD. 1150 73

The following seven polymorphic marker loci of genes responsible for predisposition to coronary atherosclerosis (CAS) were studied: the ACE locus responsible for angiotensin-converting enzyme insertion/deletion polymorphism for the presence or absence of the Alu insertion in the gene; the F13, PLAT, and APOA1 loci, controlling the clotting factor 13, plasminogen-activating tissue factor, and apolipoprotein A, respectively; the MTHFR and AGT polymorphic loci responsible for point mutations in methylenetetrahydrofolate reductase and those in angiotensinogen, respectively, and the NOS3 locus controlling the number of tandem repeats in the nitric oxide synthase gene. These loci are located on different chromosomes and encode products involved into various metabolic pathways leading to CAS. In the populations studied, significant differences between healthy subjects and patients predisposed to cardiovascular diseases were revealed with regard to the above seven markers. The 174M allele (T174M polymorphism in the ACE gene) was significantly associated with coronary atherosclerosis. It was found that specific gene combinations are involved in the CAS development and determine variation in the pathogenetically important quantitative traits.
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PMID:[Analysis of gene complexes predisposing to coronary atherosclerosis]. 1196 67

Alzheimer's disease (AD) and dementia with vascular component (DVC) are the most prevalent forms of dementia. Both clinical entities share many similarities, but they differ in major phenotypic and genotypic profiles as revealed by structural and functional genomics studies. Comparative phenotypic studies have identified significant differences in 25% of more than 100 parametric variables, including anthropometry, cardiovascular function, aortic atherosclerosis, brain atrophy, blood pressure, blood biochemistry, hematology, thyroid function, folate and vitamin B12 levels, brain hemodynamics and lymphocyte markers. The phenotypic profile of patients with DVC differs from that of AD patients in the following: anthropometric values (weight, height); cardiovascular function (ECG, heart rate); blood pressure; lipid metabolism (HDL-CHO, TGs); uric acid metabolism; peripheral calcium homeostasis; liver function (GOT, GPT, GGT); alkaline phosphatase; lactate dehydrogenase; red and white blood cells; regional brain atrophy (left temporal region, inter-hippocampal distance); and left anterior blood flow velocity. Functional genomics studies incorporating APOE-related changes in biological markers extended the difference between AD and DVC up to 57%. Brain perfusion studies show a severe brain hypoperfusion in dementia associated with enlarged age-dependent arterial perfusion times. Structural genomics studies with AD-related genes, including APP, MAPT, APOE, PS1, PS2, A2M, ACE, AGT, cFOS and PRNP genes, demonstrate different genetic profiles in AD and DVC, with an absolute genetic variation rate ranging from 30% to 80%, depending upon genes and genetic clusters. Single gene analysis identifies relative genetic variations ranging from 0% to 5%. The relative polymorphic variation in genetic clusters integrated by two, three or four genes associated with AD ranges from 1% to 3%. The main phenotypic differences between AD and DVC are genotype-dependent, especially in AD, probably indicating that different genomic factors are determinant for the expression of dementia symptoms which might be accelerated or induced by environmental and/or cerebrovascular factors.
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PMID:Phenotypic profiles and functional genomics in Alzheimer's disease and in dementia with a vascular component. 1526 64

Constitutive genomics are probably determinant for the onset of dementia in conjunction with cerebrovascular and environmental factors. Furthermore, pharmacogenomic studies predict that the therapeutic response in Alzheimer's disease (AD) is genotype-specific, and that the expression of genes involved in the regulation of drug metabolism can influence efficacy and safety issues in pharmacotherapy. AD and dementia with a vascular component (DVC = VD + MXD) are the most prevalent forms of dementia. These clinical entities share many similarities, but they differ in major phenotypic and genotypic profiles, as revealed by structural and functional genomics studies. Comparative phenotypic studies have identified significant differences in 25% of more than 100 parametric variables, including anthropometry, cardiovascular function, aortic atherosclerosis, brain atrophy, blood pressure, blood biochemistry, hematology, thyroid function, folic acid and vitamin B(12) levels, brain hemodynamics and lymphocyte markers. The phenotypic profile of patients with DVC differs from that of AD patients in the following: (a) anthropometric values, (b) cardiovascular function, (c) blood pressure, (d) lipid metabolism, (e) uric acid levels, (f) peripheral calcium levels, (g) liver function (GOT, GPT, GGT), (h) alkaline phosphatase, (i) lactate dehydrogenase, (j) red and white blood cells, (k) regional brain atrophy (left temporal region, inter-hippocampal distance) and (l) brain blood flow velocity. Functional genomics studies incorporating APOE-related changes in biological markers extended the difference between AD and DVC up to 57%. Structural genomics studies with AD-related genes, including APP, MAPT, APOE, PS1, PS2, A2M, ACE, AGT, cFOS and PRNP genes, demonstrate different genetic profiles in AD and DVC, with an absolute genetic variation rate ranging from 30 to 80%, depending upon genes and genetic clusters. Single gene analysis identifies relative genetic variations ranging from 0 to 5%. The relative polymorphic variation in genetic clusters integrated by 2, 3 or 4 genes associated with AD ranges from 1 to 3%. The main phenotypic differences between AD and DVC are genotype-dependent, especially in AD, probably indicating that different genomic factors are essential for the expression of dementia symptoms that might be accelerated or induced by environmental and/or cerebrovascular factors.
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PMID:Genomics and phenotypic profiles in dementia: implications for pharmacological treatment. 1534 38

To clarify whether the homozygous deletion (DD) genotype of angiotensin-converting enzyme gene ( ACE) is a genetic risk factor for preeclampsia in Japanese women, we performed ACE genotyping in patients with preeclampsia and healthy pregnant women, and analyzed the relationship between preeclampsia and ACE genotype, taking into account some well-known contributing factors for preeclampsia, such as primiparity, positive family history of hypertension, prepregnancy body mass index < 24, and heterozygosity and homozygosity of T235 (MT+TT) genotypes of the angiotensinogen ( AGT) gene. Among all of the subjects, the frequency of the DD genotype was not different between patients with preeclampsia and controls (16% and 12%, respectively). Regarding primiparity, prepregnancy body mass index < 24, and MT+TT genotypes of AGT, no significant differences in the frequency of the DD genotype of ACE were found between patients with preeclampsia and controls, although in a subgroup positive for family history of hypertension, the frequency of the DD genotype tended to be higher in patients with preeclampsia (25%) than in controls (8%; p = 0.061). Carrying the DD genotype may have some influence on the pathogenesis of preeclampsia, perhaps through effects on placental hypoxia or the interaction of hypertensive disease and atherosclerosis, although this influence may not be strong. Additional studies using a larger number of patients and analyses that include other genetic and environmental factors will be necessary to confirm these results.
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PMID:Insertion/deletion polymorphism of the angiotensin-converting enzyme gene and preeclampsia in Japanese patients. 1605 7

There have been many reports regarding the association between renin-angiotensin system (RAS) gene polymorphisms and coronary artery disease (CAD) or acute myocardial infarction (AMI), but the results are inconsistent. In the present study, we used several new approaches with multilocus data to reappraise this issue in a large and relatively homogeneous Taiwanese population. A total of 1254 consecutive patients who underwent cardiac catheterization (735 with documented coronary artery disease and 519 without) between 1996 and 2003 were recruited. Angiotensin-converting enzyme gene insertion/deletion (I/D) polymorphism; T174M, M235T, G-6A, A-20C, G-152A and G-217A polymorphisms of the angiotensinogen gene; and A1166C polymorphism of the angiotensin II type I receptor gene were genotyped. In single-locus analyses, no locus was associated with CAD, history of AMI and three-vessel CAD, either with or without adjustment for conventional CAD risk factors. For multilocus analyses, we recreated a balanced population, with the controls individually matched to the cases regarding the conventional CAD risk factors. We found that the angiotensinogen gene haplotype profile was significantly different between the cases and controls (chi2=31.6, P=0.030) in haplotype analyses. Furthermore, significant three-locus (G-217A, M235T and I/D) gene-gene interactions were detected by multifactor-dimensionality reduction method (highest cross-validation consistency 10.0, lowest prediction error 40.56%, P=0.017) and many even higher order gene-gene interactions by multilocus genotype disequilibrium tests (16 genotype disequilibria exclusively found in the controls, all of which included at least two genes among AGT, ACE and AT1R genes). Our study is the first to demonstrate epistatic, high-order, gene-gene interactions between RAS gene polymorphisms and CAD. These results are compatible with the concept of multilocus and multi-gene effects in complex diseases that would be missed with conventional approaches.
Atherosclerosis 2007 Nov
PMID:Renin-angiotensin system gene polymorphisms and coronary artery disease in a large angiographic cohort: detection of high order gene-gene interaction. 1711 72

Premature coronary artery disease (CAD) in subjects with type 1 diabetes dramatically affects quality of life and morbidity and leads to premature death, but there is still little known about the mechanisms and predictors of this complication. In the present study, we explored the role of genetic variants of angiotensinogen (AGT, M235T), ACE (I/D), and angiotensin type 1 receptor (ATR1, A1166C) as predictors of rapid progression of subclinical coronary atherosclerosis. Five-hundred eighty-five type 1 diabetic patients and 592 similar age and sex control subjects were evaluated for progression of coronary artery calcification (CAC), a marker of subclinical CAD, before and after a 2.5-year follow-up. In logistic regression analysis, CAC progression was dramatically more likely in type 1 diabetic subjects not treated with ACE inhibitor/angiotensin receptor blocker who had the TT-ID-AA/AC genotype combination than in those with other genotypes (odds ratio 11.6 [95%CI 4.5-29.6], P < 0.0001) and was even stronger when adjusted for cardiovascular disease risk factors and the mean A1C (37.5 [3.6-388], P = 0.002). In conclusion, a combination of genotype variants of the renin-angiotensin system genes is a powerful determinant of subclinical progression of coronary artery atherosclerosis in type 1 diabetic patients and may partially explain accelerated CAD in type 1 diabetes.
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PMID:Polymorphisms of the renin-angiotensin system genes predict progression of subclinical coronary atherosclerosis. 1759 5

Aim of the study was to investigate association of gene candidate polymorphisms encoding elements of the renin-angiotensin system and participating in regulation of vascular tone with development of microalbuminuria in patients with hypertensive disease. We examined 93 patients (52 women, 41 men, mean age 58.3+/-1.12 years, mean duration of hypertension 15.6+/-1.16 years) with hypertensive disease. Two patients had arterial hypertension (AG) with I, 22 with II, 63 with III degree of blood pressure (BP) elevation. Thirty four patients smoked, 2 had stroke in anamnesis, 33 had ischemic heart disease, in 58 heredity burdened with cardiovascular diseases was noted. In 38 patients hypertrophy of left ventricular myocardium was revealed. As gene-candidates we considered AGT, ACE, AT2R1, CYP11B2, MTHFR, PPARA, PPARG2, NOS3. Patients with microalbuminuria had significantly higher systolic and diastolic BP levels. Groups did not differ significantly according sex, age, disease duration, glucose level. There were no significant differences in involvement of other target organs - hypertrophy of left ventricular myocardium and atherosclerosis of carotid arteries. Patients with microalbuminuria had significantly higher level of blood cholesterol. Patients with and without microalbuminuria differed only in frequencies of genotypes of polymorphic marker A(-153)G of AT2R1 gene. Genotype AA predisposed to development of nephropathy--odds ratio (OR) 4.71 (95CI 1.78-12.97), while genotype AG was protective (OR 0.20 95%CI 0.07 to 0.56, p=0.031). According to results of multifactorial analysis independent factors affecting increase of risk of development of nephropathy in the studied group were level of systolic BP and carriage of genotype AA of polymorphic marker A(-153)G of AT2R1 gene.
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PMID:[Genetic aspects of development of microalbuminuria in patients with hypertensive disease]. 1907 77


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